Combination pramipexole, rasagiline reduced daytime sleepiness in adults with early PD

Key takeaways:

• P2B001, a pramipexole/rasagiline combination, was similarly efficacious to pramipexole but resulted in less new-onset excessive daytime sleepiness.
• Fewer treatment-emergent adverse events were reported.

BOSTON — Treatment with an investigational combination of low-dose pramipexole and rasagiline led to less excessive daytime sleepiness and fewer adverse events compared with pramipexole alone in early Parkinson’s disease, research showed.

“In early Parkinson’s disease, there are many side effects associated with dopamine agonists, including excessive daytime sleepiness, hypertension and others. This combination pill allows for a high level of efficacy with a much better safety profile,” Cheryl Fitzer-Attas, PhD, MBA, president of ClinMed, told Healio at the American Academy of Neurology annual meeting. “People that are younger can continue working, older people as well won’t have the dopaminergic side effects.”

Researchers sought to determine the safety and efficacy of P2B001, an investigational, fixed-dose, extended-release, once-daily combination of pramipexole 0.6 mg and rasagiline 0.75 mg, in reducing excessive daytime sleepiness (EDS) in those with early PD.

They conducted a phase 3 study of 519 untreated adults with PD, diagnosed within the past 3 years, who were randomized to receive 12 weeks of double-blind treatment with P2B001 (n = 147), extended-release pramipexole 0.6mg (PPX, n = 144), extended-release rasagiline 0.75mg (RAS, n = 144) or marketed extended-release PPX (ER-PPX, 6-week titration, n = 72).

Researchers assessed EDS via Epworth Sleepiness Scale (ESS) and reported treatment-emergent adverse events (TEAEs), using shift analysis to determine rates of new-onset, clinically relevant EDS (from ESS 10 at baseline to >10 at week 12).

According to results, P2B001 demonstrated comparable efficacy to ER-PPX, with an approximate 8-point reduction in Unified Parkinson’s disease rating scale parts II and III (95% CI, –1.67 to 2.42), but led to significantly less daytime sleepiness.

While the percentage of patients with an ESS score of less than 10 at baseline was similar between groups (86.1-88.4%), shift analysis showed rates of new-onset EDS were highest in both the ER-PPX (mean dose, 3.2mg; 35.7%) and PPX (15.6%) groups and lowest in the P2B001 (8.5%) and RAS (6.6%) groups. When researchers compared those treated with P2B001 vs. ER-PPX, the odds for developing EDS was 0.17 (95% CI, 0.08-0.36).

Researchers also noted rates of sleepiness reported were highest with ER-PPX (31.1%), followed by PPX (18.2%), P2B001 (14.7%) and RAS (4.8%), while 6% to 7% of participants in ER-PPX, PPX and P2B001 groups reporting sleepiness-related TEAEs within the first days of treatment. These events stabilized for the PPX and P2B001 groups, but steadily increased with ER-PPX titration and maintenance therapy.

“It is another drug in the toolbox for neurologists, in particular for early Parkinson’s disease,” Fitzer-Attas said.